The long-term phase III study data add to earlier findings from the same group that showed a significant improvement in local progression-free survival with the addition of regional hyperthermia in these patients.

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The multicenter EORTC 62961-ESHO 95 trial included 329 adults with localized soft tissue sarcoma with a tumor diameter of at least 5 cm, French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grade 2 or 3, and deep to the fascia.

The patients were randomly assigned to receive neoadjuvant chemotherapy with doxorubicin, ifosfamide, and etoposide alone (n=167), or in combination with regional hyperthermia (42°C for a 60-minute period; n=162) given alongside ifosfamide on days 1 and 4 of each cycle.

During a median follow-up period of 11.3 years, 220 (67%) patients experienced disease relapse, and 188 (57%) died.

As reported in JAMA Oncology, the risk for local disease progression or death was a significant 35% lower among the patients who received regional hyperthermia compared with those who did not, with median local progression-free survival at 67.3 months versus 29.2 months.

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Furthermore, the risk for death due to disease or treatment was a significant 27% lower with the addition of regional hyperthermia, with 5- and 10-year survival rates at 62.7% and 52.6%, respectively, compared with 51.3% and 42.7% among those who received chemotherapy alone. Median survival times were 15.4 years in the chemotherapy plus hyperthermia group and 6.2 years in the chemotherapy only group.

Rolf Issels (LMU Munich, Germany) and co-investigators also point out that the “treatment effect was robust and consistent among all prespecified risk factors and stratification criteria.”

The researchers believe that their study is the first to compare neoadjuvant chemotherapy with or without regional hyperthermia in a high-risk patient population.

“As such, we should not exclude the potential therapeutic benefits [regional hyperthermia] may also have in solid tumors other than soft tissue sarcoma,” they write.

The team adds that a phase III trial investigating the approach in patients with resected pancreatic cancer is already underway, while a phase II study has shown that regional hyperthermia may benefit patients with rare pediatric, malignant nontesticular germ-cell tumors.

“Therefore, there is an urgent need to raise more interest in this treatment modality by oncologists in dedicated centers,” Issels et al conclude.

In an accompanying commentary, Mark Dewhirst and David Kirsch, both from Duke University School of Medicine in Durham, North Carolina, USA, praise the study findings and say that the data “should stimulate further clinical trials in hyperthermia, which is a field that is heating up with the implementation of technological advances and strong biological rationale.”

However they acknowledge that it is unclear how the treatment can be more widely integrated, particularly as highly skilled engineers and/or physicists are needed to run the state-of-the-art instruments that deliver hyperthermia, and insurance cover is currently limited in the USA.